Evolution of the incretin system comprehension: REVIEWS

Nikolai S.  Dedanishvili; Sarng S.  Pyurveev; Andrey G.  Vasiliev; Ekaterina G.  Batotsyrenova; Mayya A.  Nurmamedova; Aleftina A.  Kravtsova; Irina I.  Mogileva; Rodion V.  Korablev; Mariya A.  Pahomova

doi:10.56871/PED.2026.18.57.008

Evolution of the incretin system comprehension

REVIEWS

Nikolai S. Dedanishvili Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-6231-445X
Sarng S. Pyurveev Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine https://orcid.org/0000-0002-4467-2269
Andrey G. Vasiliev Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-8539-7128
Ekaterina G. Batotsyrenova Saint Petersburg State Pediatric Medical University; Scientific and Clinical Center of Toxicology named after Academician S.N. Golikov of the Federal Medical and Biological Agency https://orcid.org/0000-0003-3827-4579
Mayya A. Nurmamedova City Consultative and Diagnostic Center No. 1 https://orcid.org/0009-0006-2641-3331
Aleftina A. Kravtsova Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-0657-3390
Irina I. Mogileva Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-9559-4734
Rodion V. Korablev Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0004-5754-8437
Mariya A. Pahomova Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0002-4570-8056

Keywords:

incretin system GLP-1 GIP DPP-4 GLP-1 receptor agonists type 2 diabetes mellitus obesity инкретины GLP-1 GIP DPP-4 агонисты рецептора GLP-1 сахарный диабет 2-го типа ожирение

Abstract

The incretin system plays a central role in the regulation of glucose homeostasis and is recognized as an important therapeutic target in modern endocrinology. This review outlines the evolution of scientific concepts related to incretins, from early observations of gut-derived factors enhancing insulin secretion to the identification of key incretin hormones, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Particular attention is given to the incretin effect and its role in the regulation of postprandial glycemia. The molecular mechanisms underlying incretin action are discussed, including tissue-specific processing of proglucagon, secretion by intestinal L-cells, and receptor-mediated intracellular signaling pathways. The glucose-dependent nature of GLP-1–induced insulin secretion is emphasized as a critical factor ensuring a favorable safety profile with a low risk of hypoglycemia. Additional effects of incretins are also highlighted, including regulation of glucagon secretion, gastric motility, and feeding behavior. The review further addresses the translational progression from fundamental research to clinical application. The development of GLP-1 receptor agonists, including long-acting formulations resistant to degradation by dipeptidyl peptidase-4 (DPP-4), is considered, along with their clinical efficacy in glycemic control and body weight reduction. Current advances in incretin-based pharmacotherapy are discussed, including dual GLP-1/GIP receptor agonists and emerging multi-receptor agonists. Overall, the evolution of the incretin concept represents a successful integration of basic science and clinical medicine, leading to the development of effective therapeutic strategies for the treatment of type 2 diabetes mellitus and obesity.

Author Biographies

Nikolai S. Dedanishvili, Saint Petersburg State Pediatric Medical University

MD, Postgraduate Student, Department of Biological Chemistry, Saint Petersburg State Pediatric Medical University; address: 2 Litovskaya str., Saint Petersburg, 194100, Russia

Sarng S. Pyurveev, Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

MD, Ph D, Junior Research Associate, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine, Saint Petersburg, Russia; Assistant Professor, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Andrey G. Vasiliev, Saint Petersburg State Pediatric Medical University

MD, Ph D, Dr Med Sci, Professor, Head of the Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical Pediatric University, Saint Petersburg, Russia

Ekaterina G. Batotsyrenova, Saint Petersburg State Pediatric Medical University; Scientific and Clinical Center of Toxicology named after Academician S.N. Golikov of the Federal Medical and Biological Agency

Ph D, Dr Biol Sci, Associate Professor, Scientific and Clinical Center of Toxicology named after Academician S.N. Golikov of the Federal Medical and Biological Agency, Saint Petersburg, Russia; Associate Professor, Department of Biological Chemistry, Saint Petersburg State Pediatric Medical Pediatric University, Saint Petersburg, Russia

Mayya A. Nurmamedova, City Consultative and Diagnostic Center No. 1

MD, Head of the Consultative and Diagnostic Department, Internist, Cardiologist, City Consultative and Diagnostic Center No. 1, Saint Petersburg, Russia

Aleftina A. Kravtsova, Saint Petersburg State Pediatric Medical University

Ph D, Associate Professor, Department of Pathological Physiology with the Course of Immunopathology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Irina I. Mogileva, Saint Petersburg State Pediatric Medical University

Ph D, Associate Professor, Head of the Department of Foreign Languages with a Course of Russian and Latin, Saint Petersburg State Pediatric Medical Pediatric University, Saint Petersburg, Russia

Rodion V. Korablev, Saint Petersburg State Pediatric Medical University

MD, Ph D, Associate Professor,
Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical Pediatric University, Saint Petersburg, Russia

Mariya A. Pahomova, Saint Petersburg State Pediatric Medical University

Senior Research Associate, Research Center, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

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